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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms
BMC Physiology, Volume 11, No. 1, Article 9, Year 2011
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Description
Background: The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression. Results: We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007). Conclusions: Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population. © 2011 Lillvis et al; licensee BioMed Central Ltd.
Authors & Co-Authors
Erdman, Robert A.
United States, Danville
Geisinger Medical Center
Cox, Laura A.
United States, San Antonio
Southwest National Primate Research Center
United States, San Antonio
Texas Biomedical Research Institute
Lenk, Guy M.
United States, Detroit
Wayne State University
Elmore, James R.
United States, Danville
Geisinger Medical Center
Franklin, David P.
United States, Danville
Geisinger Medical Center
Carey, David J.
United States, Danville
Geisinger Medical Center
Lancaster, Wayne D.
United States, Detroit
Wayne State University
Tromp, Gerard C.
United States, Danville
Geisinger Medical Center
Kuivaniemi, Helena
United States, Danville
Geisinger Medical Center
Statistics
Citations: 35
Authors: 9
Affiliations: 6
Identifiers
Doi:
10.1186/1472-6793-11-9
ISSN:
14726793
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study